1. Field of the Invention
The present invention relates to small, polymeric beads and, more particularly, to linear ionene modified beads for use in binding small and large anionic compounds.
2. Description of the Prior Art
It is believed that certain clinical hemorrhagic states are associated with a heparin-like substance in the blood. In addition, the value of antiheparin agents lies also in the treatment of post-partum hemorrhage and the restoration of normal blood coagubility after open heart surgery and after hemodialysis, where administration of relatively large doses of heparin is a common practice. Protamine sulfate and toluidine blue, neither of which are free of toxic effects, are clinically used as antiheparin agents.
Polycations obtained by the Menshutkin reaction of aliphatic diamines with aliphatic dihalides or by homopolymerization or dimethylamino-n-alkyl halides are referred to as ionenes. The ionenes constitute a unique system because of their structure, their distances between positive charges, their counterions and their molecular weight can be varied systematically. They form strong, insoluble complexes with heparin, the concentration of which can be determined by a simple potentiometric titration.
Studies have shown that the heparin concentration in water in low ionic strength can be determined by following the pH changes of a heparin solution when ionenes are gradually added to it. Quantitative yields of heparin ionene complexes are obtained at the neutralization point. The amount of ionene necessary to neutralize a given amount of heparin depends on the charge density of the ionene and can be determined by means of this pH titration. In addition, this procedure also offers information of the stoichiometry of polycation polyanion complexes and on the charge density of polyelectrolytes in general.
Although most ionene structures have antiheparin activity, extensive investigations of toxicology and effects on the circulatory system in laboratory animals were carried out only with 6,3-ionene bromide referred to as "Polybrene." The latter was found to be more toxic (i.v. LD.sub.50, 28 mg/kg in mice and 20 mg/kg in rats; the i.p. LD.sub.50 in mice is 61.5 mg/kg) than toluidine blue (i.v. LD.sub.50, 45 mg/kg) and protamine sulfate (i.v. LD.sub.50, 44 mg/kg). However, cumulative i.v. doses of 6,3-ionene bromode up to 5 mg/kg as 1 percent solutions could be given rapidly to anesthetize dogs without markedly affecting either the respiration or circulation, i.e., without toxic symptoms.
Heparin offers a protective action in neutralizing the toxicity of 6,3-ionene bromide in both mice and dogs. Thus pre-treatment of mice with heparin enabled them to survive doses of three times the LD.sub.50 values with only mild toxicity symptoms.